Linagliptin (8-[(3R)-3-Amino-1-piperidinyl]-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-1H-purine-2,6-dione) acts as a dipeptidyl peptidase IV (DPP IV) inhibitor and is used for the once-daily oral treatment of type 2 diabetes.
WO2004/018468 discloses linagliptin, salts thereof, processes for the preparation of linagliptin and its salts, and the use of linagliptin and its salts for the treatment of diseases, such as, for example, type 1 diabetes, type 2 diabetes, adipositas, arthritis, and calcitonin-caused osteoporosis.
WO2007/128721 describes crystalline forms A, B, C, D and E of linagliptin and processes for preparing the crystalline forms. WO2007/128721 also discloses that linagliptin prepared according to WO2004/018468 is obtained in the form of a mixture of crystalline form A and crystalline form B.
WO2007/128724 discloses a pharmaceutical composition comprising a DPP IV inhibitor compound with an amino group or a salt thereof, a first diluent, a second diluent, a binder, a disintegrant and a lubricant. According to WO2007/128724 it has been observed, that DPP IV inhibitors with a primary or secondary amino group show incompatibilities, degradation problems, or extraction problems with a number of customary excipients such as microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium, tartaric acid, citric acid, glucose, fructose, saccharose, lactose, and maltodextrines. Though the compounds themselves are very stable, they are considered to react with many excipients used in solid dosage forms and with impurities of excipients, especially in tight contact provided in tablets and at high excipient/drug ratios. It is assumed that the amino group reacts with reducing sugars and with other reactive carbonyl groups and with carboxylic acid functional groups formed for example at the surface of microcrystalline cellulose by oxidation. These problems have been primarily observed in low dosage ranges and have been solved according to WO2007/128724 by the described pharmaceutical composition comprising a DPP IV inhibitor compound with an amino group or a salt thereof, a first diluent, a second diluent, a binder, a disintegrant and a lubricant.